Effects of MK-801 upon local cerebral glucose utilisation in conscious rats following unilateral lesion of caudal entorhinal cortex.
Local cerebral glucose utilisation was examined in 62 discrete regions of conscious rats following unilateral ibotenic acid lesion of the caudal entorhinal cortex, and subsequent pharmacological challenge with (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Fourteen days after unilateral lesion of the entorhinal cortex, there were no significant alterations in local cerebral glucose use except within the lesioned entorhinal cortex (reduced by 31% compared to sham-operated control animals). In sham-operated animals, systemic administration of MK-801 (0.5 mg/kg, i.v.) induced anatomically organised alterations in glucose use with increases in olfactory areas, subicular complex and some limbic areas (posterior cingulate cortex, mammillary body and anteroventral thalamic nucleus), and decreases in the inferior colliculus and neocortex (auditory, sensory-motor, somatosensory and frontal cortices). In animals with unilateral entorhinal cortex lesions, the metabolic response to MK-801 differed significantly from the response to the drug in sham-lesioned animals in a number of regions, viz. hippocampus, molecular layer (ipsilateral to lesion), entorhinal cortex (ipsilateral), dentate gyrus (ipsilateral), presubiculum (bilateral), parasubiculum (bilateral) and nucleus accumbens (bilateral). The ability of MK-801 to reduce glucose use in the neocortex was not altered by entorhinal cortex lesion. These data suggest that the functional consequences of non-competitive NMDA receptor blockade are dependent in some areas upon the integrity of the perforant pathway from the entorhinal cortex to the hippocampus.
Kurumaji
A
A
Wellcome Surgical Institute, University of Glasgow, U.K.
McCulloch
J
J
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002250:Carbon Radioisotopes; D003243:Consciousness; D003847:Deoxyglucose / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D002250:Carbon Radioisotopes; D007051:Ibotenic Acid; D016291:Dizocilpine Maleate; D003847:Deoxyglucose; D005947:Glucose